This study is part of the two year pilot phase of the NIMH Psychotherapy of Depression Collaborative Program. The design compares the therapeutic efficacy of 1) two forms of psychotherapy, interpersonal psychotherapy and cognitive behavior therapy, alone, 2) tricyclic antidepressant therapy with clinical management alone, 3) each psychotherapy in combination with pharmacotherapy, and 4) placebo with clinical management. Subjects will be a rigorously selected group of 72 adult, non-psychotic, non-bipolar, non-suicidal patients with Major Depressive Disorder diagnosed by RDC Criteria after extensive clinical and medical evaluation. Patients will be randomly assigned to treatment for 16 weeks with experienced psychiatrist and psychologist therapists, who for six months prior to selection, will receive standardized training and supervision and will use standardized treatment procedures, which will be monitored by trainers using audio and video recordings. Independent, blind clinical evaluations by trained evaluators using a standardized assessment battery will be performed at regular intervals during treatment and a 1-2 year follow-up period to measure clinical change in depressive and other symptoms, cognitive and social function, and therapy-related variables, in order to discriminate the differential effects of each therapy in this group of patients. Data analysis for the collaborative aspects of the study will be performed at a centrally designated site.